Water permeability of high-flux dialyzer membranes after Renalin reprocessing.

Dialysis with high-flux membranes is widely used, in part, because they are thought to increase the removal of middle molecules when compared with low-flux membranes. Dialyzer reprocessing; however, is thought to alter middle molecule clearance. Renalin, a mixture of germicidal agents, has widespread use in dialyzer reprocessing. We determined the effect of Renalin reprocessing on the water permeability of three different dialyzers of Fresenius (F80A and 200A) and Gambro (17R) manufacture using the dead-end filtration method. Two hundred and seventeen, predominantly used but some new, dialyzers were evaluated. Water permeability of the used, but not the new, dialyzers fell abruptly and dramatically with reprocessing. The permeability fell almost 70% in the F80A dialyzer after three reprocessing procedures with similar, but somewhat slower declines, seen in the other two dialyzers. We conclude that there is a decline in water permeability seen in Renalin reprocessed dialyzers. This factor and the associated change in solute clearance and ultrafiltration characteristics should be considered in assessing the effectiveness of dialyzer reprocessing.

Orbitofrontal cortex dysfunction in abstinent cocaine abusers performing a decision-making task.

Cocaine abusers demonstrate faulty decision-making as manifested by their inability to discontinue self-destructive drug-seeking behaviors. The orbitofrontal cortex (OFC) plays an important role in decision-making. In this preliminary study we tested whether 25-day-abstinent cocaine abusers show alterations in normalized cerebral blood flow (rCBF) in the OFC using PET with (15)O during the Iowa Gambling Task (a decision-making task). This task measures the ability to weigh short-term rewards against long-term losses. A control task matched the sensorimotor aspects of the task but did not require decision-making. Cocaine abusers (N = 13) showed greater activation during performance of the Iowa Gambling Task in the right OFC and less activation in the right dorsolateral prefrontal cortex (DLPFC) and left medial prefrontal cortex (MPFC) compared to a control group (N = 13). Better Iowa Gambling Task performance was associated with greater activation in the right OFC in both groups. Also, the amount of cocaine used (grams/week) prior to the 25 days of enforced abstinence was negatively correlated with activation in the left OFC. Greater activation in the OFC in cocaine abusers compared to a control group may reflect differences in the anticipation of reward while less activation in the DLPFC and MPFC may reflect differences in planning and working memory. These findings suggest that cocaine abusers show persistent functional abnormalities in prefrontal neural networks involved in decision-making and these effects are related to cocaine abuse. Compromised decision-making could contribute to the development of addiction and undermine attempts at abstinence.

Differential effects of cocaine and cocaine alcohol on neurocognitive performance.

OBJECTIVE: To investigate the dose-related effects of cocaine with or without alcohol use on the CNS by measuring performance on neurobehavioral tests. BACKGROUND: Chronic use of cocaine is associated with persistent decrements in cognitive function that are most pronounced in heavy users. Specific neurobehavioral deficits in areas such as executive function and impulsivity would make it difficult for the cocaine abuser to discontinue using drugs. Because alcohol is often used in conjunction with cocaine, the CNS effects of alcohol when taken with cocaine deserve further investigation. METHOD: The authors evaluated the dose-related effects of cocaine and alcohol use on performance in a variety of neuropsychological tests after 1 to 3 days of abstinence and again after 4 weeks of abstinence. Fifty-six chronic cocaine abusers who had used cocaine during the past 24 to 48 hours volunteered to perform a battery of neuropsychological tests on two separate occasions during a period of enforced abstinence. In addition to using cocaine, most of the volunteers consumed alcohol. Approximately half of the participants consumed more than 10 alcohol-containing drinks per week. RESULTS: After controlling for the effects of age, sex, and intelligence on performance, the authors found dose-related associations between neurobehavioral performance and cocaine dose and alcohol dose. When the influences of cocaine and alcohol on neurobehavioral performance were taken separately, cocaine and alcohol each selectively affected performance on different neurobehavioral tests after 1 to 3 days of abstinence, with these effects persisting after 4 weeks of abstinence. CONCLUSION: The concomitant use of cocaine and alcohol may have additive negative effects on the brain as compared to the use of only one of these two substances.

Sleep, anxiety, and depression in abstinent and drinking alcoholics.

A group of alcoholic men were followed-up 8 years after discharge from hospital. The interview included items on sleep, anxiety, and depression. The sample was divided into abstinent and drinking subjects. Sleep data were factor analyzed. Only the Alcohol-Abstinence Sleep Factor significantly correlated with drinking status. The Alcohol-Abstinence Sleep Factor was also the primary correlate of anxiety and depression. Fewer abstinent subjects reported anxiety and depression. Sleep variables, anxiety, and depression are considered as possible markers of relapse in persons treated for alcoholism.

Incorporating individualized quality of life measures in the evaluation of pharmacy services: the IN*COMPASS framework.

Quality of life is a fascinating field to researchers and practitioners alike. To some researchers, quality of life is of interest because it offers untold challenges in constructing instruments and capturing data necessary to answer key questions about health, disease, and treatment. For such researchers, quality of life is about statistical relationships among questions and about using questions to define the physical, social, and emotional domains of health. To other researchers, this field is about finding practical applications in policy and treatment decision making for the information provided by quality of life assessments. To these researchers, the focus of quality of life is on ways to apply knowledge of quality of life differences between groups with and without specific diseases or ways to use knowledge about how treatments affect the quality of life of various patient populations. To practitioners, quality of life is about treatment outcomes that impact individual patients' daily lives. It is the practitioner that Funderburk, Pleil, and Pathak are considering in their paper in this issue of Pharmacy Practice Management Quarterly. These authors give several important messages to practitioners seeking to serve their patients by incorporating quality of life into their practices. The key message in the paper is that to better understand and determine the impact of treatment on a patient's quality of life, it is critical to start with a baseline or reference point relevant to that patient. From that baseline or reference point, treatment decisions can be made and progress, in quality of life terms, can be evaluated. Critical questions in their framework, which is called the IN*COMPASS (Individualized Client Oriented Method for Preferred Alleviation of Sickness States) Approach, are "How are you now?" and "How would you like to be?" The authors do not endorse particular quality of life tools in their approach; rather they prescribe certain critical questions that must be answered if information captured by any quality of life tool is to be useful at the patient level. Readers should not be put off by the fancy acronym used in this paper; nor must readers be keen students of quality of life to appreciate its message. The IN*COMPASS approach is fundamental to good patient care and can be applied by practitioners with any level of understanding of and appreciation for quality of life assessments.

Controlled drinking and abstinence in alcoholic men: beliefs influence actions.

A group of alcoholic men were asked 8 years postdischarge from hospital if they could drink alcohol with control. Subjects who said "no" (the NCD group) were compared to those who said "yes" (the CD group). A majority of the NCD group had been abstinent during the year preceding the 8-year evaluation, whereas none of the CD group had been. In the model developed, troubles resulting from drinking are seen as instrumental in changes from a CD to a NCD belief. The clinical relevance of our results is discussed.

Phenylpropanolamine and blood pressure: a review of prospective studies.

The use of phenylpropanolamine (PPA) as an anorectic has provoked commentary and disagreement. Its use in the last decade has been associated with a series of adverse clinical events. As in all case reports, these associations may be noncausal, particularly in light of PPAs extensive use. We have reviewed prospective clinical trials in which the administration of PPA was planned to assess impact on blood pressure. Many of these employ sedentary, healthy volunteers but also included are studies of overweight, moderately hypertensive, and ambulatory subjects. An analysis of such studies leads us to believe that PPA is an appropriately marketed over-the-counter drug, with an acceptable margin of safety. Further, we have reanalyzed our own earlier published data, which indicate that the margin of safety may actually be increased in subjects with elevated basal sympathetic tone; eg, those who are overweight and those with slight elevations of arterial blood pressure.

Reduction of perseverative errors in patients with schizophrenia using monetary feedback.

The influence of monetary feedback on Wisconsin Card Sort Test (WCST) performance of 14 male schizophrenics was investigated. Patients were administered the test under standard instructions and with monetary feedback in counterbalanced order. Monetary reinforcement reduced perseverative errors and increased correct responses (p less than .05). These findings suggest that the WCST perseverative errors of schizophrenics reflect motivational as well as cognitive factors.

Evaluation of the abuse potential of the novel analgesic flupirtine maleate.

To evaluate the psychopharmacological effects and potential abuse liability of the novel analgesic flupirtine maleate the subjective and behavioral effects of orally administered flupirtine, lorazepam and placebo were studied in polydrug abusers. Effects were measured before and for 6 h after drug administration under double-blind conditions. At therapeutic doses flupirtine was not differentiated from placebo. Lorazepam and higher doses of flupirtine produced increases in subject-rated liking, ARCI MBG scale scores, and sedative-like effects including impaired psychomotor performance. Flupirtine, but not lorazepam, increased ratings on measures indicating dysphoric effects. The results indicate that flupirtine has some sedative-like effects but that its abuse potential is probably modest.

Zolpidem and triazolam in humans: behavioral and subjective effects and abuse liability.

Zolpidem, which is currently marketed in Europe as a hypnotic, is a short-duration imidazopyridine whose actions are mediated at the gamma-aminobutyric acid benzodiazepine receptor complex. However, zolpidem produces a variety of biochemical differences from classic benzodiazepine agonists including showing selectivity for the central BZ1 (omega 1) receptor subtype as well as showing a different pattern of distribution of binding sites. This study compared zolpidem to the benzodiazepine hypnotic triazolam in 15 healthy male volunteers with histories of sedative drug abuse. Placebo, zolpidem (15, 30 and 45 mg) and triazolam (0.25, 0.5 and 0.75 mg) were administered p.o. in a mixed sequence in a double-blind, cross-over design. The onset time with zolpidem was faster than with triazolam, with peak effects of both drugs occurring at 1 to 2 hr after administration. Both zolpidem and triazolam produced dose-related decrements in performance on various performance tasks including circular lights, reaction time, balance, number recall and the digit symbol substitution test. Both drugs also produced similar dose-related changes on various observer ratings including overall strength of drug effect. Triazolam, but not zolpidem, increased subject- and observer-rated sleepiness and produced greater impairment on a picture memory task. Zolpidem, but not triazolam, produced increases in subject ratings of various somatic symptoms (e.g., dizzy, anxious and queasy) and there were 9 days on which subjects vomited after zolpidem, but none after triazolam. Although the highest dose of both drugs was identified by subjects as being active, the highest dose of triazolam was identified as being barbiturate, benzodiazepine or alcohol, almost twice as often as the highest dose of zolpidem. Overall, this study shows that although zolpidem produces many effects in common with triazolam, it also has a unique profile of effects distinguishable from classic benzodiazepine agonists. The mechanism(s) underlying these differences is unclear, but may be related to the atypical biochemical profile of zolpidem.

Determinants of the pressor effect of phenylpropanolamine in healthy subjects.

Phenylpropanolamine (PPA) is frequently used in over-the-counter diet aids and cold medicines, In view of concern about the safety of this sympathomimetic agent, we undertook a double-blind, multicenter clinical trial to determine the factors that influence the pressor effect of short-term oral administration of PPA in healthy individuals. Eight hundred eighty-one healthy individuals in four categories of body weight were randomized to receive placebo capsules three times per day (n = 286), a 75-mg sustained-release PPA hydrochloride preparation once per day (n = 296) followed by two doses of placebo capsules, or a 25-mg immediate-release PPA hydrochloride preparation three times per day (n = 299). The median age of the study population was 28 years, 56% were men, 73% were white, and 47% were in excess of 30% above their ideal body weight. Measurements of pulse rate and supine and standing blood pressure were made 11 times during the day of PPA administration. A statistically significant but clinically unimportant pressor effect for the short-term administration of PPA was observed. The effect occurred in the first 6 hours after administration and was greater in the sustained-release group. Significant independent determinants of the pressor effect of PPA were baseline diastolic blood pressure, baseline body weight, and treatment.

Subjective profile of phenylpropanolamine: absence of stimulant or euphorigenic effects at recommended dose levels.

A total of 837 healthy volunteers presenting with various degrees of obesity participated in a large-scale, double-blind, placebo-controlled evaluation of the subjective effects of phenylpropanolamine (PPA), with particular attention to measurement of the euphoriant or stimulant potential of therapeutic doses of the compound. Dosage forms studied were PPA 75 mg sustained release, PPA 25 mg, and placebo. Subjects were recruited from four independent clinical sites. At each site, subjects were stratified according to degree of overweight (normal, mildly overweight, moderately overweight, or severely overweight) and randomly assigned to one of the three drug treatment regimens. Subjective effects were measured 11 times during the 12-hour experimental session using a short-form version of the Addiction Research Center Inventory. Data analysis did not indicate discernible subjective effects that would differentiate PPA from placebo, but did show typical circadian fluctuations. These results provided evidence that therapeutic doses of PPA do not produce the euphoriant or "stimulant" subjective effects that characterize drugs of abuse.

Relative abuse liability of lorazepam and diazepam: an evaluation in 'recreational' drug users.

The subjective, psychomotor and cognitive effects of oral doses of lorazepam (0, 1.5, 3 and 6 mg) and diazepam (0, 10, 20 and 40 mg) were studied under double-blind conditions in 14 volunteers with histories of 'recreational' benzodiazepine use/abuse. For each subject, drug was administered over 4 test days in a 2 (drug) by 4 (dose level) mixed design. Drug was the between-groups factor while dose was the within-subjects factor. Test days were separated by at least 1 week. The results showed that subjective ratings of drug 'liking' and the psychomotor and cognitive effects of lorazepam were generally similar to those of diazepam over the range of doses studied. Lorazepam, however, tended to produce effects of longer duration than diazepam. Since previous studies have shown that diazepam has a relatively high abuse liability among the benzodiazepines, the present findings suggest that lorazepam shares this property with diazepam is subjects with a history of 'recreational' drug use/abuse.

Locating and interviewing alcoholics 8 years after discharge from hospital.

An 8-year follow-up of 85 alcoholic men resulted in 93% interviewed or confirmed deceased. The location and interview techniques used to achieve this high completion rate are reported and the "location" of deceased subjects is discussed. A list of the agencies that might have information on the whereabouts of subjects is provided. The time course of data collection is analyzed. The characteristics of subjects lost under specific follow-up inadequacies or constraints are considered. Our findings can be used by program evaluators as a basis for decisions concerning the best use of their follow-up resources.

Phenylpropanolamine: effects on subjective and cardiovascular variables at recommended over-the-counter dose levels.

Two controlled clinical studies evaluated the effects of phenylpropanolamine HCL (PPA) on measures of blood pressure, pulse, and subjective state (mood). One hundred fifty subjects participated in a parallel groups design that compared a 75-mg sustained release (SR) preparation with a 25-mg tid. dosing regimen and placebo. Fifty-nine of these subjects participated in an additional cross-over component that compared SR PPA 75 mg with placebo. Measures of blood pressure, pulse, and subjective drug effect were obtained nine times throughout the course of a 12-hour session. Data analysis revealed no clinically and few statistically significant effects due to drug treatment. As expected, most measures showed circadian changes on both the cardiovascular and mood variables, which were not related to drug treatment. No euphorogenic or "amphetamine-like" effects were noted. Although further work is warranted regarding the effects of chronic or higher-than-normal doses of PPA, the current studies suggest that PPA, at currently recommended dose levels, is not associated with adverse effects on either cardiovascular or subjective functioning.

The characteristics of alcoholics frequently lost to follow-up.

In a follow-up of 85 alcoholic men, 93% were interviewed or confirmed deceased 8 years after discharge from hospital. The sample was also followed up at 1 and 3 years postdischarge. Follow-up rates of other published studies are discussed. Scales to assess difficulty of interview and difficulty of location were developed. Factor analysis revealed the differential characteristics of subjects defined as difficult to locate, difficult to interview or missing. Subjects who are difficult to locate, or who in the extreme case will go missing, tended to have poorer social functioning prior to intake and to be residentially unstable during the follow-up period, characteristics that tend to correlate with worse drinking outcome. Subjects who are unwilling to be interviewed tended to be residentially stable and show better interpersonal adjustment at follow-up. Less intensive location procedures would have resulted in data loss from those classified as difficult to locate. Less persuasive interview techniques would have resulted in data loss from those classified as difficult to interview. Early termination of the follow-up would also have resulted in data loss from the latter group. The distinct types of data biases that would be introduced by loss of information from each of the above subgroups are examined.

Mortality and illness in male alcoholics: an 8-year follow-up.

An 8-year follow-up was conducted on a group of male alcoholics. Their mortality and illness records were examined. The number of observed deaths is 4.7 times that expected. The excess deaths appear to be due to causes frequently associated with alcoholism. Patient characteristics predictive of mortality are presented. Inpatient stays in general hospitals, for reasons other than alcoholism, totaled almost four times the duration expected. The relationships between drinking patterns and hospitalizations are studied. Clinical tests, which show improvement in response to abstinence, are suggested as positive reinforcers for patients in alcoholism treatment.